Process for the preparation of n-carbamoyloxyphenyl carbamates

ABSTRACT

The specification discloses the production of herbicidal Ncarbamoyloxyphenyl carbamic acid esters and a process for the production thereof in which an N-hydroxyphenyl carbamate is added to a reaction mixture comprising phosgene and an amine.

United States Patent Boroschewski Aug. 26, 1975 [5 PROCESS FOR THEPREPARATION OF [51] Int. CL. C07C 125/06 N-CARBAMOYLOXYPHENYL [58] FieldOf Search 260/47l C, 472 CARBAMATES [75] Inventor: Gerhard Boroschewski,Berlin, [56] References cued Germany OTHER PUBLICATIONS [73] Assignee:Schering Aktiengesenschafi, Adams, P. et 3]., Chemical Reviews, Vol 65(1965) Bergkamen, Germany QD 1A page [22] Filed: Primary Examiner-AntonH. Sutto App]. No.: 339,977

Related US. Application Data Continuation-impart of Ser. No. 669,697,Sept. 22, 1967. abandoned.

Assistant ExaminerL. A. Thaxton Atlorney, Agent, or Firm-Joseph F.Padlon [57] ABSTRACT The specification discloses the production ofherbicidal N-carbamoyloxyphenyl carbamic acid esters and a process forthe production thereof in which an N- hydroxyphenyl carbamate is addedto a reaction mixture comprising phosgene and an amine.

2 Claims, No Drawings PROCESS FOR THE PREPARATION OFN-CARBAMOYLOXYPHENYL CARBAMATES This is a continuation in part of myco-pending application, Ser. No. 669,697 filed 9/22/67 now abandoned.

The instant invention is directed to the production ofN-carbamoyloxyphenyl carbamates by a single-step reaction in which anN-hydroxyphenyl carbamate is added directly to a reaction mixturecomprising phosgene and an amine. The desired product is recovereddirectly from the resulting reaction mixture in good yields andsubstantially free of reaction by-products and impurities.

The compounds produced by the reaction herein described have the generalformula and structure:

wherein R,, R and R are individually selected from the group consistingof aliphatic radicals, cycloaliphatic radicals, arylaliphatic radicals,aromatic radicals, and heterocyclic radicals. Aliphatic radicals may besubstituted by heterocyclic groups and the remaining groups may carryone or more halogen atoms, alkyl, haloalkyl, alkoxy, or alkylmercaptogroups. In addition to the above, R, and R, can be hydrogen or whentaken together with the amino-nitrogen can form a heterocycle which maycontain oxygen atoms or additional nitrogen atoms. R, and R areindividually selected from the group consisting of hydrogen andaliphatic radicals.

In preferred embodiments of the invention R, and R are hydrogen, loweralkyl, haloalkyl, alkaryl, or cycloalkyl. R, can be alkyl, preferablylower alkyl, aryl, pref erably phenyl, alkaryl or alkenyl, preferablyallyl. R, can be hydrogen, aliphatic or lower alkyl. R can be hydrogenor lower alkyl. As used herein the term lower alkyl refers to straightor branched chain alkyl groups having from 1 to about 6 carbon atoms.

The above described compounds have been found useful in the control ofweeds and undesirable plants and have hereto fore been prepared byreaction of carbamic acid chlorides or isocyanates and N- hydroxyphenylurethanes. These procedures are disadvantageous however, because of thelimited number of compounds which can be prepared. For example, whenisocyanates are employed only compounds having a monosubstitutedcarbamoyl moiety can be prepared, i.e., either R, or R above, must behydrogen. Disubstituted compounds require an additional alkylation stepwhich introduces a possibility of alkylation of the other nitrogen atom.Anhydrous reaction conditions are usually required in order to avoiddecomposition of the isocyanatc.

In the instant process the above described compounds can be convenientlyprepared in a single reaction mixture and without recovery ofintermediates by a process in which an N-hydroxyphenyl urethane of theformula is added to a reaction mixture comprising phosgene and aselected amine having the formula wherein R, through R,, are definedabove, R,,- is hydrogen or an aliphatic radical, preferably a loweralkyl group, and X is hydrogen, a monovalent metal, preferably an alkalimetal or an ammonium group having one or more N-alkyl substituents.

Use of the above described process provides a means of preparing thedesired products from known N- hydroxyphenyl urethanes and amines underconvenient conditions and most importantly without the necessity ofrecovering and further reaction of intermediates. Another importantadvantage of the above described process is that the final product isobtained in high yields without substantial by-product production or thepresence of substantial amounts of impurities resulting from thechemical reaction itself.

The process of the instant invention employs N- hydroxyphenyl urethaneswhich may be derived from primary or secondary alcohols or from phenols.Aliphatic alcohols, cycloaliphatic and arylaliphatic are useful and cangenerally carry various substituents such as halogen atoms, alkylradicals, haloalkyl radicals, and alkoxy, or alkylmercapto groups. Amongthe most preferred compounds are lower alkyl, such as methyl, ethyl,propyl, and isopropyl; m-butyl, sec. butyl, and tort. butyl. Alsosuitable are beta-chloroethyl, ally] and butynel -yl-3-urethanes.

In place of the n-hydroxyphenyl urethane, per se, there can be usedsalts formed by reaction of the urethane with alkali hydroxides, aqueousammonia, or amines which may be primary, secondary, or tertiary andalkyl or aromatic.

Illustrative amines include aniline, N-methylaniline, 2-, 3- and4-chloroaniline, 4-fluoroaniline, 4- bromoaniline, 4-iodoaniline, 2-, 3-and 4-toluidine, 2,3- dimethyl aniline, 2,4-dimethyl aniline, 3-trifluoromethyl aniline, N-ethyl-4-toluidine, methylamine, ethylamine,propylamine, isopropylamine, butylamine, isobutylamine, see-butylamine,tert.- butylamine, hexylamine, oetylamine, trimethylamine,triethylamine, l-methyll -ethyl-amylamine, 2,2- dimethylpropylamine,N,N-dimethylaniline and N,N- diethylaniline and others.

The above-described process is carried out in solution in which thesolvent is an organic solvent e.g., chlorinated hydrocarbons, esters,nitriles and ethers. Specific examples of suitable solvents are aceticester, acetonitrile and dioxane.

The reaction can be carried out at temperatures ranging from 0C. toabout C. and preferably from room temperature to about 100C. Once thereaction has been completed, the reaction mixture is worked up usingstandard procedures for separation of solvent phases and precipitationor crystallization of reaction products. Generally, salts which form canbe separated by filtration or addition of suitable amounts of waterwhich is later separated from the organic phase. The organic phase isrecovered and dried and finally evaporated under reduced pressure. Theuse of ice water to facilitate crystallization from the organic phase isoften advantageous. It is also advantageous to carry out the reaction inthe presence of an acid acceptor agent such as one of theabove-described amines or an alkali carbonate e.g., sodium carbonate, ortriethylamine.

The reaction products are generally colorless crystalline materials, asdescribed below, which have good herbicidal properties.

The following examples illustrate the practice of the instant invention.

The N-hydroxyphenylurethanes useful as starting materials can beprepared by the procedure shown in Example I, following.

EXAMPLE 1 21.8 g (0.2 mole) m-aminophenol and 5 g magnesium oxide aredispersed in 70 ml. water and 70 ml. ethyl acetate. The mixture iscooled to C. whereupon 26.5 g (0.2 mole) butin-( l )-yl-(3)-chloroformate is added drop by drop and stirring is continued forminutes at room temperature. Thereafter the excess of magnesium oxide isdissolved in dilute hydrochloric acid, and the organic phase is washedwith a little water and thereafter with dilute potassium bicarbonatesolution until neutral. After drying over desiccated sodium sulfate andevaporation of the ethyl acetate in a vacuum, the crude product ispurified by dissolving it in a little ether, filtering the ethersolution, and crystallizing the butin-( l )-yl-( 3)-N-( 3-hydroxyphenyl)-carbamate by addition of petroleum ether.

Table 1, following shows additional compounds, having structure ll,which have been prepared by the pro- Salts of these derivatives whereinX has the meaning If monovalent metal e.g., sodium or potassium, are ob:ained by adding a calculated amount of metal hydroxde or metalmethylatc to a solution of the derivative for example in methanol), andsubsequent evaporaion in a vacuum. The salts with ammonia, N-ilkylamines, N,N-dialkylamines, and N.N.N- rialkylamines need not berecovered for the subseuent reaction. it is preferred to employsolutions vhich contain molar amounts of the hydroxyphenyurethanes andof the amine.

EXAMPLE 2 Production of methyl-N-(3-(N "(3 -methylphenyl)-carbamoyloxy)-phenyl)carbamate 20.3 g (0.205 mole) of phosgene are dissolved in 40 ml.of dioxane. To this solution is added in drops while cooling at about 20to 25C., a solution of 21.4 g (0.2 mole) of m-toluidine, 42.5 g (0.42mole) of triethylaminc and 33.4 g (0.20 mole) of methyl-N-( 3-hydroxyphenyl) carbamate in 100 ml. of dioxane while stirring. Themixture is heated to C. for 30 minutes. After cooling, it is poured intoiced water. The separated oil crystallizes upon trituration with purewater and is purified by washing with a little ether.

Yield: 52.6 g 87.7% of the theory F 139 to 142C.

EXAMPLE 3 Production of ethyl-N-( 3-( N'-methyl-N '-phenylcarbamoyloxyphenyl)carbamate In a solution of 9.89 g (0.1 mole) of phosgene in 50ml. of dioxane, there is added in drops while stirring at 20 to 25C., asolution of 18.1 g (0.1 mole) of ethyl-N- (3-hydroxyphenyl) carbamateand 24.2 g (0.2 mole) of N,Ndimethyl aniline in 50 m1. of dioxane. Themixture is then boiled for 90 minutes with reflux, and poured into icedwater after cooling, the resultant carbamate is extracted with ether,and the ether solution washed with dilute soda lye and iced water anddried with magnesium sulfate. After evaporation of the ther, theearbamate crystallizes upon addition of light gasoline.

Yield: 26.7 g of the theory F 103 to 104C.

The following compounds have been prepared by the procedures disclosedherein.

It will be noted that the symbol F in the table below represents themelting point (MP).

Com pound No. Name of Compound Physical Constant F=l 511-1 5 1CContinued -Continucd Compound Name of Compound Physical Cunstun! F= l60C C (Impound Name of Compound Physical Conslzml phenylcarbumoyloxy)carhumutc dichlnrophenyl )-Curbumnylnxy phenyl )curbumalc -ContinucdC0ntinucd Compound Name of Cnmpuuntl Ph \sicul Constant l-ll methIcurhamoyloxy )-6-mcthylmcthylphenyl )-curhamoyloxy I mcthylphenyll-curhumuyloxy phenyUcnrham-ute methylphcnyl l-curhumoyloxy phcnylJcurhamutc mcthylphenyl I-curbnmoylnxy phcnyl lcurhumatc Methyl-N434 N-methyI-N 43 F l 44- l 45C F, 136-] am I-l, 127 I ZB C Compound Name ofCompound Physical Constant F, I 23-1 24, c

What is claimed is:

I. A process for preparing N-carbamoyloxyphcnyl carbamates of theformula T('OOR:1 l

wherein X can be hydrogen or an alkali metal and R R and R are asdefined above with an amine of the formula

1. A PROCESS FOR PREPARING N-CARBAMOYLOXPHENYL CARBAMATES OF THE FORMULA2. The process of claim 1 wherein the organic solvent is selected fromthe group consisting of dioxane, acetic ester and acetonitrile.